Tablets having discontinuous coated regions

ABSTRACT

A dosage form comprising a tablet core and one or more discontinuous coated regions in various configurations on the surface of the dosage form is disclosed. A method for making the dosage form is also disclosed.

This application claims priority of the benefit of the filing of U.S.Provisional Application Ser. No. 62/364,059, filed Jul. 19, 2016, thecontents of which are hereby incorporated by reference in theirentirety.

FIELD OF THE INVENTION

The present invention relates to a dosage form comprising a tablet core,preferably in compressed form, that has a coating over a portion of itsexterior surface. The coating preferably is in the form of one or morediscontinuous coated region. The one or more discontinuous coatedregions appear on the dosage form in various configurations. The one ormore discontinuous coated regions confer a number of benefits to thedosage form including, but not limited to, the ability to add actives,colors, flavors, sensates and textures; improved swallowability;perception of speed, taste masking, and visual recognition to aid inproduct selection. The present invention also relates to apparatus thatmay be used to apply the one or more discontinuous coated regions on thedosage form.

BACKGROUND OF THE INVENTION

Capsules had long been recognized as a preferred dosage form for theoral delivery of active ingredients, which may be in the form of powder,liquid or granules of different compositions, for delivery to thegastro-intestinal tract of a human. Advantages of capsules as a dosageform include the variety of shapes and color combinations (includingdifferent colored caps and bodies), enhancing their uniqueidentification, their glossy elegant appearance, and their easyswallowability. One type of commonly used capsule is a two-piece hardshell capsule, typically made from gelatin, starch, or cellulosederivatives. The hard shell capsule typically comprises a longer bodyhaving an outside diameter, and a relatively shorter cap having aninside diameter that will fit over the outside diameter of the body. Thecap fits snugly over the body, creating an overlapping portion of thecapsule.

In view of the tamperability of old-fashioned capsules made with hardshell capsule halves of different diameters which can be taken apart,steps have been taken since the 1980s, to manufacture capsule shellswhich, once assembled, cannot be disassembled without their destruction.One such example is the Capsugel CONI-SNAP® capsule, which has groovesthat lock the cap and body together after the capsule has been filled.Another such example is the Parke-Davis KAPSEAL® capsule, in which thebody and cap are sealed together using a discontinuous coated region ofgelatin. Although the sealing or discontinuous coated banding of capsuleshell halves has, in a large part, proven effective to at least maketampering evident to the consumer, some companies have preferred tomanufacture solid dosage forms having densely compacted cores to furtherreduce the possibility of tampering.

One of the first types of film-coated elongated compressed tablets wasreferred to as a “caplet”. The caplet form offered enhancedswallowability over uncoated tablets due to its elongated shape. Whilecaplets are still popular today, the next generation of dosage forms,which offered all of these advantages of the capsule, comprised denselycompacted cores that were coated with gelatin or similar glossymaterials, typically in two parts having different colors. U.S. Pat.Nos. 5,089,270; 5,213,738; 4,820,524; 4,867,983 and 4,966,771 representdifferent approaches to providing a capsule-shaped product in the formof an elongated tablet having a coating, which provides the appearanceand, therefore, the consumer acceptability of the previously popularcapsule.

U.S. Pat. Nos. 5,415,868 and 5,317,849 disclose different manners bywhich either hard shell capsule halves can be shrink-wrapped onto atablet (the '868 patent) or a tablet core covered at opposite ends witha soft gelatin capsule shell half and subsequently dried to simulate acapsule-like medicament (the '849 patent). U.S. Pat. No. 5,464,631discloses that studies have also shown the functional importance toconsumers of providing a capsule-appearing solid dosage form, which ismulti-colored. The utilization of two colors functionally identifies thetype of medication as well as provides a capsule-appearing product witha psychologically perceived medicinal efficacy. Aesthetically, also,consumers apparently prefer the attractive appearance of multi-coloredcapsules to single colored capsules.

For purposes of the invention, a gelatinous material is defined to be amaterial that, when applied to a surface of a dosage form, produces afilm coating having a surface gloss comparable to gelatin coatings.Preferably, the gelatinous coating has a surface gloss greater thanabout 150, more preferably greater than about 200.

Gelatins have served as coating material. Hence, the phrase “gelatinous”material. Work has been done to expand the range of materials capable ofproviding the desired glossy finish that contain substantially nogelatins.

U.S. Pat. Nos. D500,849; D506,544; D525,356; 7,879,354; 8,067,029; andU.S. Pat. No. 8,815,290 to Johnson & Johnson Consumer Inc. disclose adosage form that comprises a core having an exterior surface and firstand second ends and comprising one or more active ingredients; a firstgelatinous coating over at least part of the core; and a secondgelatinous coating over at least part of the core.

U.S. Pat. No. 5,534,263 to Alza Corporation discloses a dosage form thatis useful for prolonged delivery of an active agent. The dosage form isa matrix with two or more insoluble bands on its surface. The referencediscloses that, according to an embodiment, the two or more bands dropoff the matrix as it erodes, and that according to another embodiment,the surface area between the two or more bands, which are fixed on thematrix, erodes.

Canadian Patent No. 2,540,044 to Alza Corporation discloses a dosageform that provides controlled release of an active agent. The referencediscloses that the dosage form contains a reservoir that containsactive; an engine partially within the reservoir; and a soluble orinsoluble band provided over an outer surface of the engine and thereservoir that binds the engine to the reservoir.

International Published Application No. WO2006099618 to Dr. Reddy'sLaboratories Ltd. discloses a dosage form that comprises a substratecontaining an active agent and a solid component deposited onto areas ofa surface of the substrate that also contains an active agent. Thereference discloses that the solid component may containpharmaceutically acceptable excipients, including, e.g., colorants,flavors, taste-masking agents and the like. The reference discloses thataccording to an embodiment, a band may be applied to the surface andthat areas on the surface that receive the band may be recessed.According to an embodiment, a band surrounds the circumference of atablet.

U.S. Pat. No. 8,252,234 to Smithkline Beecham Corporation discloses anapparatus for producing a pharmaceutical product that contains a doseinspection device, wherein the dose inspection device performs opticalprofilometry on a carrier substrate to determine an amount of activeingredient that has been added to the carrier substrate.

U.S. Pat. Nos. 8,122,149 and 8,101,244 to SmithKline Beecham Corporationdiscloses an apparatus for producing a pharmaceutical product thatcontains a dose inspection system, wherein the dose inspection systemcontains a camera, wherein the camera takes an image of a dosage ofactive agent while being applied to a carrier substrate.

U.S. Pat. Nos. 8,123,509 and 7,638,081 to SmithKline Beecham discloses amold that contains a cavity in which a core may be located, wherein thecore has a space to define a shape and dimension of coating to be placedon the core.

U.S. Published Applications Nos. 20160032909 and 20150190834 to GlaxoSmithKine disclose a method and a device for dispensing fluid from apump that includes dispensing a first volume of fluid through an outletport to form a pendant droplet in the outlet port; dispensing a secondvolume of fluid though the outlet port; and ejecting a full droplet fromthe outlet port, wherein the full droplet volume is the sum of the firstdroplet volume and the second droplet volume.

U.S. Pat. Nos. 8,986,777 and 8,967,074 to SmithKine disclose a devicefor dispensing a fluid onto a target that contains a porous band havinga hollow interior positioned so that the end of the dispensing nozzle isin the hollow interior to form a gap between the inner surface of thehollow band and the end of the dispensing nozzle.

There continues to be a need in the pharmaceutical industry to provideover-the-counter coated dosage forms which simulate the appearance ofcapsules and which identify the source and type of medication providedso that the consumer can readily identify, for example, if the productis a particular type of analgesic or whether it includes antihistaminesor other active ingredients in combination with analgesics. Such soliddosage forms have preferably been in the shape of an elongated tablet,and are identified as gelcaps when a solid elongated core is coveredwith a gelatinous covering or geltabs where the core is in the shape ofa round tablet with a gelatinous coating.

The present invention furthers these earlier advances by producing animproved gelcap or geltab relative to the commercially availablegelatinous coated products.

In accordance with the invention, gelatinous discontinuous coatedregions are used to provide similar benefits as coating, while providinga new appearance and the ability to vary the types of materials used inthe discontinuous coated regions, preferentially on a compressed orcoated compressed dosage form. Use of the discontinuous coated regionsin accordance with the invention provides advantages, including but notlimited to, permitting the addition of actives, colors, flavors,sensates and textures; improving swallowability; providing a perceptionof speed; permitting taste masking; and providing for visual recognitionto aid in product selection.

SUMMARY OF THE INVENTION

Tablet compression and coating are two of the most critical aspects ofpharmaceutical dosage form manufacturing, since these are the mainaspects of the product discernable to the patient consuming the product.Tablet compression tooling is typically designed to produce tablets freeof visual defects to the extent permitted by the composition of thetablet and the equipment used in the manufacturing process. Identifyingmarks and symbols engraved into the tablet surface during compressionare generally designed in adherence with established guidelines forshape, size, depth, wall angles, corner rounding, spacing, etc. of thecharacters to minimize the introduction of defects into debossed designsand to produce legible identification on the tablet followingcompression and/or coating. In its desired form, batch tablet coating isperformed in a manner yielding a homogenous coating appearance free ofvisual defects and irregularities. When properly applied, conventionaltablet coating equipment (e.g., coating pans, fluidized bed coaters,etc.) are designed to minimize heterogeneity of the resultant coatedtablets, and post-coating processing, including, but not limited to,surface printing, gelatin dipping, overlayer placement, and laserdrilling, is required to introduce, or give the appearance of,heterogeneous regions on the tablet surface.

The dosage form of the invention may be coated using methods including,but not limited, to carrier tray coating, spray coating, dip coating,enrobing, electrostatic deposition and/or 3D printing.

The techniques described herein provide a demonstrated method ofpreparing solid dosage forms on conventional tablet preparationequipment containing visually identifiable features on the tabletsurface that will intentionally produce heterogeneous regions of coatingdeposition upon conventional tablets.

Other features and advantages of the present invention will be apparentfrom the detailed description of the invention and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram showing examples of common tablet shapes, Tablets &Capsules, November 2011, Copyright CSC Publishing.

FIG. 2 is a diagram showing a standard caplet 1.

FIGS. 3A-3F are photographs showing standard caplets 1 coated with twolongitudinal discontinuous coated regions 2 in accordance with anembodiment of the invention.

FIG. 4 is a photograph showing a standard caplet 1 coated with threecircumferential discontinuous coated regions 2 in accordance with anembodiment of the invention.

FIGS. 5A and 5B are photographs showing standard caplets 1 coated withthree circumferential discontinuous coated regions 3, wherein two endcircumferential discontinuous coated regions 3 a and 3 b each cover aportion of the end portions of the caplet, in accordance with anembodiment of the invention.

FIGS. 6A and 6B are diagrams showing a standard convex tablet 601 coatedwith a circumferential discontinuous coated region 3 over a substantialportion of the standard convex tablet 601, in accordance with anembodiment of the invention. FIGS. 6C and 6D are diagrams showingapparatus that may be used to prepare the coated tablet shown in FIGS.6A and 6B. The circumferential discontinuous coated region 3 of FIG. 6Ais applied with the aid of a fixture apparatus FIG. 6C, 620 which isdesigned to engage depressed features FIGS. 6A and 6B, 603 a and 603 b,which are located on both sides of the standard convex tablet 601. Thestandard convex tablet 601 is thus able to rotate about the axis throughthe depressed features 603 a and 603 b enabling the circumferentialcoating of the standard convex tablet 601 by a conformal coating wheelFIG. 6C, 621. Any movable surface that would permit rotation and coatingof the tablet is envisioned to be within the scope of the presentinvention. For example, a movable surface with a non-circular geometrymay be employed as a “coating wheel” to better coat substrates havingcorresponding non-circular geometry. A face of the movable surface canhave any configuration to assist with corresponding tablet having variedconfiguration. FIGS. 6C and 6D are diagrams of the fixture apparatus 620and conformal coating wheel 621. When movable pins FIG. 6D, 630 engageinto the depressed features 603 a and 603 b of the standard convextablet 601 an axis of rotation is enabled. The rotation of conformalcoating wheel 621 which is covered in coating solution (not shown)induces rotation and subsequent circumferential application of materialonto the standard convex tablet 601. The shear behavior of the coatingfluid (not shown), the shear rate which is determined by the rotationalspeed and diameter of the conformal coating wheel 621 and the viscosityof the coating solution (not shown) create a force which inducesrotation of the standard convex tablet 601.

FIG. 6E is an alternate embodiment of the invention where standardconvex tablet 601 has a hole 604 that can be used to enable an axis ofrotation around a pin 640. FIG. 6F is another embodiment of theinvention where the standard convex tablet 601 has a non-circularperimeter 605. FIG. 6G is a further embodiment of the invention wheredepressions 606 in the standard convex tablet 601 coincide with theregion of the standard convex tablet 601 covered by the conformalcoating wheel 621. These depressions 606 are of sufficient depth toavoid being coated by the coating solution. The standard convex tablet601 then has the appearance shown in FIG. 6H.

FIG. 7A is a diagram showing a standard caplet 1 coated with alongitudinal discontinuous coated region 2, wherein the longitudinaldiscontinuous coated region 2 contains one or more openings 703, inaccordance with an embodiment of the invention. FIG. 7B is a photographshowing the dosage form of FIG. 7A.

FIG. 8 is a diagram showing the dimensions of a standard caplet 1 coatedwith three circumferential discontinuous coated regions 3, wherein twoend circumferential discontinuous coated regions 3 a and 3 b each covera portion of the end portions of the caplet, in accordance with anembodiment of the invention.

FIGS. 9A-9C are diagrams showing various carrier trays 190 that can beused to apply one or more circumferential discontinuous coated regions 3to a dosage form in accordance with an embodiment of the invention.

FIGS. 10A-10C are diagrams showing a segmented coating wheel 622, whichcontains one or more drive rings FIG. 10B, 180 and 181, that can be usedin combination with carrier trays 190 and a bath FIG. 10A, 182 to applyone or more circumferential discontinuous coated regions (not shown) toa dosage form in accordance with an embodiment of the invention. FIG.10B shows drive ring 180 and 181 features. The purpose of the driverings 180 and 181 are to disrupt the boundary fluid layer and create ameans to achieve rotation of the standard caplet 1. Without these driverings 180 and 181, the hydrostatic effect of the fluid film acts similarto a fluid bearing which can prevent proper rotation. The drive rings180 and 181 minimize this effect by piercing the fluid and creatingmechanical engagement with the standard caplet 1.

As the standard caplet 1 is conveyed by means of the carrier tray 190into proximity of the segmented coating wheel 622 the coating fluid 182which is distributed around the circumference of the segmented coatingwheel 622 begins to coat the standard caplet 1. The rotation of thesegmented coating wheel 622 and the shear force induced by the viscosityof the coating fluid 182 induces rotation of the standard caplet 1 andsubsequent circumferential discontinuous coated region coating of thestandard caplet 1. The lift height “X”, the diameter of the segmentedcoating wheel 622 and the linear velocity of the carrier tray 190determine the rotational velocity of the standard caplet 1 and theduration of time the standard caplet 1 is rotated.

FIG. 11 is a diagram showing a coating wheel 621 that can be used incombination with a carrier tray 190 and the drive rings 180, 181 toapply one or more longitudinal discontinuous coated regions (not shown)to a dosage form in accordance with an embodiment of the invention.

FIGS. 12A-12G are diagrams showing an embodiment that permits coating ofnon-rounded horizontally compressed caplets 1 a. FIG. 12A shows thecarrier tray 190, the conformal coating wheel 621, which contains one ormore drive rings (not shown), and the coating fluid bath 182 in action.The conformal coating wheel 621 dips into the coating fluid bath 182containing coating fluid 183. A roller wheel 194, also known as a movingabutment face, which runs along the conformal coating wheel 621 prior tothe carrier tray 190, may be employed to assist with rolling ofnon-rounded caplets 1 a. The carrier tray 190 moves along the edge ofthe conformal coating wheel 621 to permit coating of a portion of thenon-rounded caplet 1 a. A capillary filament holder 195 can be employedto ensure a straight coated area with clean edges. FIG. 12B showsdirection of rotation of a non-rounded caplet 1 a when the carrier tray190, the conformal coating wheel 621 and the coating bath (not shown)are in action. FIG. 12C shows a means for driving the roller wheel 194using a motorized friction belt system 196. FIG. 12D shows the carriertray 190 with roller wheel 194 without the motorized friction beltsystem 196. FIGS. 12E and 12F show the capillary filament holders 195which help to create a straight and uniform edge of the discontinuouscoated region by using capillary action to distribute the coating fluidover the peaks and valleys on the non-circular cross section of thehorizontally compressed caplet. FIG. 12G shows a dosage form prepared inaccordance with the embodiment(s) set forth in FIGS. 12A-12-F.

In the embodiments of this invention described thus far, the geometry ofthe coating discontinuous coated regions are constrained by tablet andcaplet geometry, the direction of feed that the tablet or caplet ispresented to the coating wheel and the geometry of the coating wheelitself. In order to remove these restrictions of coating geometry and toimprove the accuracy of the amount of coating applied for surfaceapplication of drug, an alternate embodiment of the invention has beendeveloped. In this embodiment an intermediate applicator has beendesigned to both accurately control the volume of coating material andto independently control the geometry of the coating on the tablet.Since the shape of the applicator, a circle, square or polygon forexample, can be selected independently from the shape of the tablet,greater freedom and precision of coating are obtained. For theapplication of one or more drugs to regions on the surface of a tabletor gum, precise control of the coating fluid dose weight is of paramountimportance to be in compliance with pharmaceutical regulation, i.e.,cGMP guidelines. In order to aid in the goal of high precision doseaccuracy, a feature of a preferred embodiment of the invention is use ofvolumetric spacing features on the surface of the applicator. Thesefeatures when engaged against a tablet/caplet housed in a spring loadedcarrier assure that a fixed volume of drug containing coating isdeposited during each application. Since the tablet is contained in aspring loaded and floating carrier, size variations which are commonlyencountered in manufacturing are negated and therefore do not adverselyaffect the dose accuracy.

FIGS. 13A-13C are diagrams of intermediate applicator geometries. FIG.13A-FIG. 13C are views of circular intermediate applicators 201 showingarrangements of volumetric spacing features 404. Of note with thesearrangements is that the geometries are vented such that when chargedwith fluid the entrained air can escape between the volumetric spacingfeatures 404. (An enclosed ring would entrap an air bubble so thisgeometric arrangement was created to prevent this occurrence.) Thesurface area (πr2 in the case of circular geometries) of the applicatorand the length “A” of the volumetric spacing features 404 are selectedto control the volume of fluid coating material. Surface tension of thefluid around the volumetric spacing features 404 create a levelingeffect which also contributes to uniformity of fluid distribution acrossthe face of the applicator 405 and aids in achieving accurate dosing.

FIGS. 14A-14F outline the sequence of steps for charging theintermediate applicator 201 with fluid and depositing the fluid onto thesurface of the tablet or gum medicament 202. FIG. 14A depicts a heatedcoating fluid bath 182 with an inner bath that establishes an accurateand constant fluid level established by the outlet of the coating fluidreservoir 183. Intermediate applicator 201 is heated by means of fluidconnections 198 and 199. FIG. 14B depicts intermediate applicator 201being immersed into the coating fluid bath 182 up to the surface 405 ofthe intermediate applicator 201. FIG. 14C shows the intermediateapplicator 201 now charged with fluid at the surface 405 of theintermediate applicator 201. FIG. 14D depicts a tablet or gum medicament202 seated in a spring loaded carrier 203. The carrier spring loaded 203and spring 204 are designed to compress as well as accommodate angularmisalignment such that the tablet or gum medicament 202 can seat againstthe intermediate applicator 201 regardless of surface imperfections orseating irregularities. FIG. 14E depicts the intermediate applicator 201compressing the tablet or gum medicament 202 against the spring 204 thusassuring that the volumetric spacing features 404 control the gap andtherefore the volume and geometric distribution of coating fluid 183 onthe surface of the tablet or gum medicament 202. Any object(s) thatpermit(s) axes of freedom such that the surface of the tablet or gummedicament 202 conforms to the volumetric spacing features 404 isenvisioned to be within the scope of the present invention. FIG. 14Fdepicts the intermediate applicator 201 after fluid application. Ingeneral, for most coating fluids 183 and most non-absorbent tablets orgum medicaments 202 half of the coating fluid 183 remains on theintermediate applicator 201 and half of the coating fluid 183 isdeposited on the surface of the tablet or gum medicament 202 as adiscontinuous coated region [ ]. Since the fluid viscosity is controlledand unchanging this is highly repeatable and factored into the dosagecalculations. Absorbent tablets or gum medicaments 202 would deviatefrom this 50:50 ratio depending on the absorbency of the tablet or gummedicament 202 material and the duration of time that the applicatorremains in contact with the surface.

FIG. 15 is a diagram of a dosage form coated using the embodimentdisclosed in FIGS. 14A-14F

FIG. 16 is a diagram of a high speed continuous motion coating apparatus249 using an alternate embodiment of the intermediate applicator coatingmethod. In FIG. 16, a single lane of medicaments 258 is shown beingcoated for clarity; however a production scale implementation could havemultiple lanes of product for higher outputs. In this embodiment, thechallenge of getting fluid from a stationary coating bath onto acontinuously moving applicator and a continuously moving conveyingsystem containing tablets/gums is addressed. In this embodiment, arotary fluid transfer wheel 250 is introduced. This rotary fluidtransfer wheel 250 is immersed into coating fluid bath 182 with a doseadjust doctor blade 252. The dose adjust doctor blade 252 is adjusted tocontrol the amount of fluid coating the rotary fluid transfer wheel 250which picks up a coating of fluid on its circumference as it rotates inthe coating fluid bath 182. The rotary fluid transfer wheel 250 issynchronously connected to applicator wheel 253 such that at the fluidtransfer zone 254 the tangential velocities of the two wheels arematched. The applicator wheel 253 has applicators 255 that are on acircular pitch that precisely matches the pitch of the tablet conveyor260. The applicator wheel 253 is also synchronously connected to thetablet conveyor 260 such that the applicator tips 257 precisely line upwith the tablet or gum medicaments 258 contained in the conveyor links259.

FIG. 17 is a graph showing the results of the viscosity testing forExamples 1-3.

FIGS. 18 and 19 illustrate a cross sectional view of an embodiment ofthe invention where a dosage form 300 is constructed with three layersof material 301, 302, and 303 which are applied to the surface of asubstrate 304 in a series of sequential steps using several applicatorsystems. Each layer of material that is applied to the substrate (e.g.,tablet, gum or lozenge) may have distinct physical properties such as,e.g., level of solubility, density, flavor, opacity/translucence, andcolor. Different active agents, flavors or sensates can be contained ineach layer and incompatible active agents, flavors or sensates can beseparated by an intermediate barrier layer. In combination with themanipulation of the solubility of the carrier material the releaseprofile of the various layers can each be individually controlled. Forexample, a burst release effect can be achieved when an erosion matrixtablet, gum or lozenge is coated with an immediate release layer ofmaterial which is subsequently encapsulated or overcoated by an erosionor slowly soluble outermost layer. When either the outermost later orthe erosion matrix tablet is dissolved to the point where the immediaterelease layer is exposed, this layer can quickly solubilize to createthe desired burst release effect. In the case of a gum or lozenge,saliva would be the solubilizing fluid and the bust release would occurin the mouth. In the case of a swallowable dosage form, gastric fluidswould be the solubilizing agent and the bust release would occur in thestomach.

In summary, the use of the applicator system allows each layer to have adifferent pattern, a different thickness, a different volume and adifferent surface area to control both the appearance and level ofencapsulation of the preceding layer or layers. The layers are notconstrained to be of uniform thickness or to cover continuous areas asis common with conventional pharmaceutical coating technologies such aspan coating and enrobing. The use of an applicator system havingvolumetric spacing features enables precision and control of fluiddosing and fluid volume. This, in combination with chilled active agentcan create a rapid set molded region.

FIGS. 20-30 illustrate the use of several applicator systems to preparethe dosage form described in FIGS. 18 and 19. In this embodiment, acompressed tablet 400 with a depressed region 401 is used as a substratefor the coating layers. A substrate such as a similarly shaped lozengeor a gum could also be used. The substrate can alternatively be porouswhich allows the deposited liquid material to penetrate a distance intothe core of the tablet through capillary action. The construction of thedosage form starts with the application of a first layer of solventcontaining or a hot melt coating material 402 such as erythritol to thesurface of the compressed tablet 400 using an intermediate applicator403 with optional volumetric spacing features 404. This first coating isallowed to cool and solidify, or in the case a solvent containingmaterial, the solidification occurs after removal of the solvent. Theintermediate applicator 403 contains a fluid passage 406 for heatingfluid to enable precise temperature control of the intermediateapplicator 403 to keep hot melt or gelling materials in a flowable stateabove their melting point. In a preferred embodiment, the intermediateapplicator 403 has a tip geometry that conforms to the shape of thedepressed region 401 of the tablet 400. This enables a uniform coatingthickness across the tablet surface. An applicator with a non-conformalgeometry can alternatively be used to create a coating of varyingthickness. The first coating step is illustrated in FIG. 20.

FIG. 21 illustrates the second application of the liquid fill material.Intermediate applicator 410 with optional volumetric spacing features404 deposits the liquid fill material 411 into the coated depressedsurface 412 of the compressed tablet 400. After removal of theintermediate applicator 410 the liquid fill deposit 413 remains in therecessed depression 401.

FIG. 22 illustrates the final encapsulation layer application.Intermediate applicator 420 deposits encapsulation material 421 over thesurface of the previously applied liquid fill 413. The diameter (orsurface area for non-circular geometries) of the intermediate applicatortip is greater than the diameter of the liquid fill deposit 413 suchthat the overlap can create a perimeter seal around the liquid fillmaterial.

FIGS. 23 through 26 illustrate a 3-D representation of the processespreviously described.

FIGS. 27 through 30 illustrate a 3-D cross sectional view of theprocesses previously described.

FIG. 31 illustrates an alternative embodiment where a pump 500 is usedin combination with an intermediate applicator 501 to accomplish thedeposition of coating material to the substrate surface. As has beenpreviously described, the intermediate applicator 201 was charged usinga fluid bath 200 (see FIG. 14). The use of the fluid bath methodologyhas a drawback when highly viscous materials are required as coatingmaterial due to poor flow behavior. By eliminating the fluid bath as ameans of charging the applicator and substituting a precision meter pump500 to inject coating material directly to the tip of the applicatorthrough a fluid passageway 502, highly viscous materials can beaccurately deposited. A positive displacement meter pump 500 isconnected to an intermediate applicator 501 with fluid passageway 502via tubing 503. The intermediate applicator 501 also contains volumetricspacing features 504 which set a fixed volume cavity for accurate dosingon the surface of the substrate. A preset volume of viscous coatingmaterial 505 is injected via the positive displacement meter pump 500into the cavity 507 created by the volumetric spacing features 504 andthe surface of the medicament 202. This volumetric cavity establishesthe geometry and shape of the coating material on the tablet surface.

FIG. 32 illustrates the intermediate applicator 501 with fluidpassageway 502 withdrawing from the surface of the substrate.

DETAILED DESCRIPTION OF INVENTION

As used herein, the term “dosage form” applies to any solid compositiondesigned to contain a specific pre-determined amount (dose) of a certainingredient, for example an active ingredient as defined below. Suitabledosage forms may be pharmaceutical drug delivery systems, includingthose for oral administration, buccal administration, rectaladministration, topical or mucosal delivery, or subcutaneous implants,or other implanted drug delivery systems; or compositions for deliveringminerals, vitamins and other nutraceuticals, oral care agents,flavorants, and the like. In a particularly preferred embodiment, thedosage form is an orally administered system for delivering apharmaceutical active ingredient to the gastro-intestinal tract of ahuman. In another preferred embodiment, the dosage form is an orallyadministered “placebo” system containing pharmaceutically inactiveingredients, and the dosage form is designed to have the same appearanceas a particular pharmaceutically active dosage form, such as may be usedfor control purposes in clinical studies to test, for example, thesafety and efficacy of a particular pharmaceutically active ingredient.

As used herein the term “tablet” refers to a solid form prepared bycompaction of powders on a tablet press, as well known in thepharmaceutical arts. Tablets can be made in a variety of shapes,including round, or elongated, such as flattened ovoid or cylindricalshapes. Examples of common tablet shapes are shown in FIG. 1. As usedherein, a “caplet core” refers to one type of elongated, generallycylindrical or capsule-shaped tablet having straight or slightly bowedsides, and a generally circular cross-section, and having a length todiameter ratio from about 2 to about 5, e.g., from about 2.5 to about3.5, say about 3.

A caplet is one type of elongated tablet covered by a film coating. Anexample of a standard caplet is shown in FIG. 2. Referring to FIG. 2, acore 10 in the shape of an elongated tablet has two ends 12 at opposingsides of a longitudinal axis. A belly band 14 may occur along thelongitudinal circumference where the tablet is in contact with die wallsduring compaction.

The core can have any number of pharmaceutically acceptable tabletshapes. Tablet is meant to encompass shaped compacted dosage forms inthe broadest sense and should not be limited to the shapes shown inFIG. 1. An elongated tablet is a type of tablet having an elongatedshape. One type of caplet core shown in FIG. 2 has a generally circularcross section that generally tapers from the mid-section to a tip or endregion. For purposes of this application, the longitudinal axis passesthrough the center of both ends of the caplet core.

The core (or substrate) may be any solid form. The core may be preparedby any suitable method, for example the core be a compressed dosageform, or may be molded. As used herein, “substrate” refers to a surfaceor underlying support, upon which another substance resides or acts, and“core” refers to a material that is at least partially enveloped orsurrounded by another material. For the purposes of the presentinvention, the terms may be used interchangeably: i.e., the term “core”may also be used to refer to a “substrate.” Preferably, the corecomprises a solid, for example, the core may be a compressed or moldedtablet, hard or soft capsule, suppository, or a confectionery form suchas a lozenge, nougat, caramel, fondant, or fat based composition.

In one embodiment, the core has one or more major faces. The core may bein a variety of different shapes. For example, in one embodiment thecore may be in the shape of a truncated cone. In other embodiments thecore may be shaped as a polyhedron, such as a cube, pyramid, prism, orthe like; or may have the geometry of a space figure with some non-flatfaces, such as a cone, cylinder, or the like. Exemplary core shapes thatmay be employed include tablet shapes formed from compression toolingshapes described by “The Elizabeth Companies Tablet Design TrainingManual” (Elizabeth Carbide Die Co., Inc., p. 7 (McKeesport, Pa.))(incorporated herein by reference) as follows (the tablet shapecorresponds inversely to the shape of the compression tooling):

-   -   Shallow Concave.    -   Standard Concave.    -   Deep Concave.    -   Extra Deep Concave.    -   Modified Ball Concave.    -   Standard Concave Bisect.    -   Standard Concave Double Bisect.    -   Standard Concave European Bisect.    -   Standard Concave Partial Bisect.    -   Double Radius.    -   Bevel & Concave.    -   Flat Plain.    -   Flat-Faced-Beveled Edge (F.F.B.E.).    -   F.F.B.E. Bisect.    -   F.F.B.E. Double Bisect.    -   Ellipse.    -   Oval.    -   Capsule.    -   Rectangle.    -   Pentagon.    -   Octagon.    -   Diamond.    -   Arrowhead.    -   Bullet.    -   Barrel.    -   Half Moon.    -   Shield.    -   Heart.    -   Almond.    -   Parallelogram.    -   Trapezoid.    -   FIG. 8/Bar Bell.    -   Bow Tie.    -   Uneven Triangle.

The core may be pressed of a blend of suitable active ingredients andexcipients which may be either their natural color, including white, orcan be conventionally colored as desired to provide a core of anydesired color.

According to an embodiment, the core may contain a disintegrant and/or asuperdisintegrant. Suitable disintegrants for making the core, or aportion thereof, by compression, include, e.g., sodium starch glycolate,cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose,starches, microcrystalline cellulose, and the like. According to anembodiment, the superdisintegrant is present as a percentage of theweight of the core from about 0.05 percent to about 10 percent.

The dosage form of the present invention preferably contains one or moreactive ingredients. Suitable active ingredients broadly include, forexample, pharmaceuticals, minerals, vitamins and other nutraceuticals,oral care agents, flavorants and mixtures thereof. Suitablepharmaceuticals include analgesics, anti-inflammatory agents,antiarthritics, anesthetics, antihistamines, anti-smoking agents,antitussives, antibiotics, anti-infective agents, antivirals,anticoagulants, antidepressants, antidiabetic agents, antiemetics,antiflatulents, antifungals, antispasmodics, appetite suppressants,bronchodilators, cardiovascular agents, central nervous system agents,central nervous system stimulants, decongestants, oral contraceptives,diuretics, expectorants, gastrointestinal agents, migraine preparations,motion sickness products, mucolytics, muscle relaxants, osteoporosispreparations, polydimethylsiloxanes, respiratory agents, sleep-aids,urinary tract agents and mixtures thereof.

Suitable flavorants include menthol, peppermint, mint flavors, fruitflavors, chocolate, vanilla, bubblegum flavors, coffee flavors, liqueurflavors and combinations and the like.

Examples of suitable gastrointestinal agents include antacids such ascalcium carbonate, magnesium hydroxide, magnesium oxide, magnesiumcarbonate, aluminum hydroxide, sodium bicarbonate, dihydroxyaluminumsodium carbonate; stimulant laxatives, such as bisacodyl, cascarasagrada, danthron, senna, phenolphthalein, aloe, castor oil, ricinoleicacid, and dehydrocholic acid, and mixtures thereof; H2 receptorantagonists, such as famotidine, ranitidine, cimetadine, nizatidine;proton pump inhibitors such as omeprazole or lansoprazole;gastrointestinal cytoprotectives, such as sucraflate and misoprostol;gastrointestinal prokinetics, such as prucalopride, antibiotics for H.pylori, such as clarithromycin, amoxicillin, tetracycline, andmetronidazole; antidiarrheals, such as diphenoxylate, loperamide andracecadotril; glycopyrrolate; antiemetics, such as ondansetron,analgesics, such as mesalamine.

Examples of suitable polydimethylsiloxanes, which include, but are notlimited to dimethicone and simethicone, as disclosed in U.S. Pat. Nos.4,906,478, 5,275,822, and 6,103,260, the contents of each which isexpressly incorporated herein by reference. As used herein, the term“simethicone” refers to the broader class of polydimethylsiloxanes,including but not limited to simethicone and dimethicone.

In one embodiment of the invention, at least one active ingredient maybe selected from bisacodyl, famotidine, ranitidine, cimetidine,prucalopride, diphenoxylate, loperamide, lactase, mesalamine, bismuth,antacids, and pharmaceutically acceptable salts, esters, isomers, andmixtures thereof.

In another embodiment, at least one active ingredient is selected fromanalgesics, anti-inflammatories, and antipyretics, e.g., non-steroidalanti-inflammatory drugs (NSAIDs), including a) propionic acidderivatives, e.g., ibuprofen, naproxen, ketoprofen and the like; b)acetic acid derivatives, e.g., indomethacin, diclofenac, sulindac,tolmetin, and the like; c) fenamic acid derivatives, e.g., mefenamicacid, meclofenamic acid, flufenamic acid, and the like; d)biphenylcarbodylic acid derivatives, e.g., diflunisal, flufenisal, andthe like; e) oxicams, e.g., piroxicam, sudoxicam, isoxicam, meloxicam,and the like; f) cyclooxygenase-2 (COX-2) selective NSAIDs; and g)pharmaceutically acceptable salts of the foregoing.

In one particular embodiment, at least one active ingredient is selectedfrom propionic acid derivative NSAID, which are pharmaceuticallyacceptable analgesics/non-steroidal anti-inflammatory drugs having afree —CH(CH₃)COOH or —CH₂CH₂COOH or a pharmaceutically acceptable saltgroup, such as —CH(CH₃)COO-Na+ or CH₂CH₂COO—Na+, which are typicallyattached directly or via a carbonyl functionality to a ring system,preferably an aromatic ring system.

Examples of useful propionic acid derivatives include ibuprofen,naproxen, benoxaprofen, naproxen sodium, fenbufen, flurbiprofen,fenoprofen, fenbuprofen, ketoprofen, indoprofen, pirprofen, carpofen,oxaprofen, pranoprofen, microprofen, tioxaprofen, suprofen,alminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, andpharmaceutically acceptable salts, derivatives, and combinationsthereof. In one embodiment of the invention, the propionic acidderivative is selected from ibuprofen, ketoprofen, flubiprofen, andpharmaceutically acceptable salts and combinations thereof. In anotherembodiment, the propionic acid derivative is ibuprofen,2-(4-isobutylphenyl) propionic acid, or a pharmaceutically acceptablesalt thereof, such as the arginine, lysine, or histidine salt ofibuprofen. Other pharmaceutically acceptable salts of ibuprofen aredescribed in U.S. Pat. Nos. 4,279,926, 4,873,231, 5,424,075 and5,510,385, the contents of which are incorporated by reference.

In another particular embodiment of the invention, at least one activeingredient may be an analgesic selected from acetaminophen, acetylsalicylic acid, ibuprofen, naproxen, ketoprofen, flurbiprofen,diclofenac, cyclobenzaprine, meloxicam, rofecoxib, celecoxib, metamizolsodic (dypirone), caffeine, and pharmaceutically acceptable salts,esters, isomers, and mixtures thereof.

In another particular embodiment of the invention, at least one activeingredient may be selected from phenylephrine, pseudoephedrine,phenylpropanolamine, chlorpheniramine, carbinoxamine, doxylamine,dextromethorphan, diphenhydramine, astemizole, terfenadine,fexofenadine, loratadine, desloratadine, cetirizine, acetylcysteine,guaifenesin, carbocysteine, ambroxol, bromhexine, mixtures thereof andpharmaceutically acceptable salts, esters, isomers, and mixturesthereof.

In another particular embodiment, the at least one active ingredient isan NSAID and/or acetaminophen, and pharmaceutically acceptable saltsthereof.

In another embodiment, the at least one active ingredient is nicotineand related salts including but not limited to nicotine tartrate. Incertain embodiments, the nicotine in any form is selected from the groupconsisting of the free base form of nicotine, a nicotine salt, anicotine derivative, such as a nicotine cation exchanger, a nicotineinclusion complex or nicotine in any non-covalent binding, nicotinebound to zeolites, nicotine bound to cellulose or starch micro spheres,and mixtures thereof. Numerous nicotine salts are known, and may beused, e.g., the salts presented in Table 1, and preferably monotartrate,hydrogen tartrate (also called bitartrate or bitartrate dihydrate),citrate, malate, and/or hydrochloride

In one embodiment, the core contains nicotine. In another embodiment,the core contains 2-4 mg of nicotine and the applied discontinuouscoating region contains 1-3 mg of additional nicotine. In anotherversion of this embodiment, the band is applied to one face of the form,wherein the face containing the immediate release of nicotine is appliedto the mucosal surface, for instance buccal surface of the oral cavity.

In one embodiment the form of the present invention includes a methoddelivering nicotine and/or metabolites thereof, such as cotinine,nicotine N′-oxide, nornicotine, (S)-nicotine-N-β-glucuronide andmixtures, isomers, salts and complexes thereof as well as use andproduction of said formulations. Nicotine and/or metabolites thereof,such as cotinine, nicotine N′-oxide, nornicotine,(S)-nicotine-N-β-glucuronide and mixtures, isomers, salts and complexesthereof in any form and/or a nicotine-mimicking compound may be includedin one or several portions of the dosage form.

One embodiment of the present invention is thus to provide an efficientand effective product, as well as methods and systems to deliver forexample nicotine and/or metabolites thereof, such as cotinine, nicotineN′-oxide, nornicotine, (S)-nicotine-N-β-glucuronide and mixtures,isomers, salts and complexes thereof and/or a nicotine-mimickingcompound and optionally component/components for creating anorganoleptic sensation to a subject so as to obtain a transmucosaluptake of nicotine and/or metabolites thereof, such as cotinine,nicotine N′-oxide, nornicotine, (S)-nicotine-N-β-glucuronide andmixtures, isomers, salts and complexes thereof in the oral cavity of thesubject. Thus, the present invention provides a method for deliveringfor example nicotine and/or metabolites thereof, such as cotinine,nicotine N′-oxide, nornicotine, (S)-nicotine-N-β-glucuronide andmixtures, isomers, salts and complexes thereof in any form to a subjectcomprising administering to a subject an oral formulation containingnicotine and/or metabolites thereof, such as cotinine, nicotineN′-oxide, nornicotinc, (S)-nicotine-N-β-glucuronide and mixtures,isomers, salts and complexes thereof in any form into the oral cavity ofthe subject and if needed allowing the nicotine and/or metabolitesthereof, such as cotinine, nicotine N′-oxide, nornicotine,(S)-nicotine-N-β-glucuronide and mixtures, isomers, salts and complexesthereof in any form in the oral formulation to be released in the salivain the oral cavity and absorbed into the systemic circulation of thesubject as well as a method for producing said oral formulation.

In one embodiment the dosage form may also comprise a suitable system ofbuffering agent/s to facilitate nicotine administration. In oneembodiment the buffering agent is added to the coating and the immediaterelease portion of nicotine is added to the discontinuous coated region.In another embodiment the buffering agent is added to one discontinuouscoated region, and the immediate release nicotine portion is added to asecond discontinuous coated region. In another embodiment the bufferingportion is added to a discontinuous coated region and the immediaterelease portion of nicotine is added to the coating. Absorption ofnicotine from the oral cavity to the systemic circulation is dependenton the pH of the saliva, pH of the blood plasma and the pKa of nicotine,which is about 7.8, Thus, the level and type of buffering agent/s orcombination thereof will affect the pH of the saliva and hence theabsorption of nicotine in a free base form, which is the formpredominantly absorbed through the mucosa.

The buffering is designed so as to achieve a transient buffering of thesaliva of a subject during melting, disintegration or dissolution of theoral formulation. As the change is transient, the pH will return to itsnormal value after a certain period of time.

The buffering agent may be but is not limited to buffering agentsselected from the group consisting of carbonate (including bicarbonateor sesquicarbonate), trometamol(2-amino-2-hydroxymethyl-1,3-propanediol, and also referred to astromethamine, tris(hydroxymethyl aminomethane and TRIS), gtycinate,different phosphate systems such as trisodium phosphate, disodiumhydrogen phosphate; and tripotassium phosphate, dipotassium hydrogenphosphate, glycerophosphate or citrate of an alkali metal (such aspotassium or sodium, or ammonium), e g trisodium and tripotassiumcitrate, different hydroxides, amino acids, and mixtures thereof.

The active ingredient or ingredients are present in the dosage form in atherapeutically effective amount, which is an amount that produces thedesired therapeutic response upon oral administration and can be readilydetermined by one skilled in the art. In determining such amounts, theparticular active ingredient being administered, the bioavailabilitycharacteristics of the active ingredient, the dosing regimen, the ageand weight of the patient, and other factors should be considered, asknown in the art. Typically, the dosage form comprises at least about 1weight percent, preferably, the dosage form comprises at least about 5weight percent, e.g., about 20 weight percent of one or more activeingredients. In one preferred embodiment, the core comprises a total ofat least about 25 weight percent (based on the weight of the core) ofone or more active ingredients.

The active ingredient or ingredients may be present in the dosage formin any form. For example, one or more active ingredients may bedispersed at the molecular level, e.g., melted or dissolved, within thedosage form, or may be in the form of particles, which in turn may becoated or uncoated. If an active ingredient is in the form of particles,the particles (whether coated or uncoated) typically have an averageparticle size of about 1-2000 microns. In one preferred embodiment, suchparticles are crystals having an average particle size of about 1-300microns. In another preferred embodiment, the particles are granules orpellets having an average particle size of about 50-2000 microns,preferably about 50-1000 microns, most preferably about 100-800 microns.

In a preferred embodiment, the dissolution characteristics of the atleast one active ingredient follow an “immediate release profile”. Asused herein, an immediate release profile is one in which the activeingredient dissolves without substantial delay or retardation due to thedosage form. This can be contrasted with the dissolution of modifiedrelease, e.g., delayed or controlled release dosage forms known in theart. In one embodiment, the dissolution rate of the immediately releasedactive ingredient from the dosage form of the invention is within about20% of the dissolution rate of the active ingredient from a purecrystalline powder of said active ingredient, e.g., the time for 50%,75%, 80%, or 90% dissolution of active ingredient from the dosage formis not more than 20% longer than the corresponding time for 50%, 75%,80%, or 90% dissolution of active ingredient from a pure crystallinepowder of said active ingredient. In another embodiment, the dissolutionof the immediately released active ingredient from the dosage form ofthe invention meets USP specifications for immediate release tablets,gelcaps, or capsules containing the active ingredient. For example, foracetaminophen tablets, USP 24 specifies that in pH 5.8 phosphate buffer,using USP apparatus 2 (paddles) at 50 rpm, at least 80% of theacetaminophen contained in the dosage form is released therefrom within30 minutes after dosing; and for acetaminophen and codeine phosphatecapsules USP 24 specifies that at least 75% of the acetaminophencontained in the dosage form is dissolved within 30 minutes in 900 mL of0.1 N Hydrochloric acid using USP Apparatus 2 (paddles) at 50 rpm; andfor ibuprofen tablets, USP 24 specifies that in pH 7.2 phosphate buffer,using USP apparatus 2 (paddles) at 50 rpm, at least 80% of the ibuprofencontained in the dosage form is released therefrom within 60 minutes.See USP 24, 2000 Version, 19-20 and 856 (1999). In yet anotherembodiment, the immediately released active ingredient is acetaminophen,and when tested in 37° C. water using USP Apparatus II (paddles) at 50rpm, at least 80%, preferably at least 85%, of the acetaminophencontained in the dosage form is released therefrom within 30 minutes.

In yet another embodiment, the time for release of at least 80%,preferably at least 85%, of at least one active ingredient contained inthe dosage form is released therefrom is not more than about 50%, e.g.,not more than about 40% of the time specified by the dissolution methodfor immediate release listed in the United States New Drug Applicationfor that particular active ingredient.

In one particularly preferred embodiment, when the immediately releasedactive ingredient is acetaminophen, when tested in 37° C. water usingUSP Apparatus II (paddles) at 50 rpm, at least 80% of the acetaminophencontained in the dosage form is released therefrom within about 6minutes, e.g., within about 5 minutes, or within about 3 minutes.

In one embodiment the tablet and coating positions can be observed usingthe USP Disintegration test as outlined in USP 34—NF29, Section 701. Inanother embodiment the tablet and coating positions can be observed byplacing the tablet into water at 37° C. without agitation.

According to an embodiment, disintegration of the tablet withoutagitation can be observed at less than about 30 seconds, e.g., less thanabout 15 seconds, e.g., less than about 10 seconds, e.g., less thanabout 5 seconds.

In certain preferred embodiments, the core is covered with a coatingthat can be any number of medicinally acceptable coverings. The use ofcoatings is well known in the art and disclosed in, for example, U.S.Pat. No. 5,234,099, which is incorporated by reference herein. Anycomposition suitable for film-coating a tablet may be used as a coatingaccording to the present invention. Examples of suitable coatings aredisclosed in U.S. Pat. Nos. 4,683,256, 4,543,370, 4,643,894, 4,828,841,4,725,441, 4,802,924, 5,630,871, and 6,274,162, which are allincorporated by reference herein. Suitable compositions for use ascoatings include those manufactured by Colorcon, a division of BerwindPharmaceutical Services, Inc., 415 Moyer Blvd., West Point, Pa. 19486under the tradename “OPADRY®” (a dry concentrate comprising film formingpolymer and optionally plasticizer, colorant, and other usefulexcipients). Additional suitable coatings include one or more of thefollowing ingredients: cellulose ethers such ashydroxypropylmethylcellulose, hydroxypropylcellulose, andhydroxyethylcellulose; polycarbohydrates such as xanthan gum, starch,and maltodextrin; plasticizers including for example, glycerin,polyethylene glycol, propylene glycol, dibutyl sebecate, triethylcitrate, vegetable oils such as castor oil, surfactants such asPolysorbate-80, sodium lauryl sulfate and dioctyl-sodium sulfosuccinate;polycarbohydrates, pigments, opacifiers.

Preferred coatings include water soluble polymers selected from thegroup consisting of hydroxypropylmethyl cellulose, hydroxypropylcellulose, methyl cellulose, polymethacrylates, polyvinyl alcohol,polyvinyl alcohol:polyethylene glycol copolymers and mixtures thereof.

According to an embodiment, the average thickness of the coating ispreferably in the range from about 1 to about 150 microns, or from about50 to about 90 microns, or from about 10 to about 90 microns, or fromabout 20 to about 80 microns, or from about 30 to about 70 microns.

In one embodiment, the coating comprises from about 10 percent to about50 percent, e.g., from about 15 percent to about 20 percent of HPMC. Thedried coating typically is present in an amount, based upon the dryweight of the core, from above about 0 percent to about 5 percent, orfrom about 1 percent to about 4 percent, or from about 2 percent toabout 3 percent, or from about 1 to about 2 percent. The coatingcomposition is optionally tinted or colored with colorants such aspigments, dyes and mixtures thereof.

In one embodiment, a layer of coating is applied to the entire exteriorsurface of core prior to application of one or more discontinuous coatedregions. Coating can be applied as a clear, transparent coating suchthat the core can be seen. The choice is dictated by the preference ofthe manufacturer and the economics of the product. In a preferredembodiment, a commercially available pigment is included the coatingcomposition in sufficient amounts to provide an opaque film having avisibly distinguishable color relative to the core.

The discontinuous coated regioned tablet of the invention provides anobservable means of differentiation. The term “observable” (and formsthereof such as “observably,” “observing,” etc.) is intended to have itscommon meaning, i.e., perceptible (or “perceptibly,” perceiving,” etc.as appropriate) using any one or more of the five human senses, e.g.,sight, sound, touch, taste and smell. The discontinuous coated regionedtablet described herein can employ interaction with one or more of thefive senses, and particularly may employ visual, audible and tactileinteraction or combinations thereof. Preferably, the discontinuouscoated regioned tablet employs interaction with the visual sense.

The discontinuous coated regioned tablet of the invention can provide amechanism by which consumers are provided with criteria that arerelevant to appropriate selection or deselection of a given product. Forexample, the discontinuous coated regioned tablet is presented to theconsumer and the consumer simply visually observes decision criteria andselects or deselects a product based on the criteria. Any type of designwhich functions as a cue as described herein is encompassed by theinstant invention.

The “criteria” will have relevance to the decision-making process fordeciding whether or not a product is appropriate for, and thereforecould be purchased and used by, a consumer considering using theproduct. Since different criteria for use will apply to differentproducts, the criteria will vary depending on the product beingmarketed. Examples of criteria include but are not limited to drug,location of symptoms, symptoms treated, time of day for use,drowsy/non-drowsy, form, flavor and combinations thereof.

Criteria as used herein includes both single (i.e., criterion) andmultiple (i.e., criteria) characteristics on which a decision may bebased. Therefore, criteria may include single or multiplecharacteristics which are relevant to the decision making process.

Each of the selectable responses will be either positively associatedwith appropriate purchase and use of the product by a consumer (i.e., apositive selectable response), or negatively associated with appropriateuse (i.e., a negative selectable response) and therefore would beassociated with deselection of the product.

The term “selection indicia” is intended to mean any observable symbolwhich is either positively associated with appropriate purchase and useof the product, i.e., positive selection indicia, or negativelyassociated with appropriate purchase and use of the product, i.e.,negative selection indicia. Selection indicia include observable symbolssuch as graphic symbols including color coding, alphanumeric graphics,pictorial graphics and the like, and sounds such as musical notes,bells, audible language and the like, and combinations thereof. Theselection indicia are chosen to be compatible with the design of thediscontinuous coated regioned tablet.

For the sake of brevity, the term “indicia” as used herein includes bothsingle symbols (i.e., indicium), such as a single color or graphic, andcombinations of symbols (i.e., indicia), such as stripes of alternatingcolors or a specific color background with a pictorial and/oralphanumeric graphic in the foreground, and the like. Therefore, asingle selection indicia may be comprised of one symbol or a combinationof symbols which, when observed together as a whole, serve as a singlepositive or negative selection indicia.

In one embodiment the dosage form of the present invention is amultilayer tablet, e.g., a trilayer tablet or a bilayer tablet. In afurther embodiment the bilayer tablet comprises a modified or sustainedrelease layer and an immediate release layer.

In one embodiment, the discontinuous coated region is comprised of amaterial that is melted and solidifies upon application of thediscontinuous coated region. In this embodiment, the discontinuouscoated region may cool and harden at room temperature or upon cooling ata temperature less than 25° C. Suitable low-melting hydrophobicmaterials include polymers, meltable carbohydrates, fats, fatty acidesters, phospholipids, and waxes. Examples of suitable fats includehydrogenated vegetable oils such as for example cocoa butter,hydrogenated palm kernel oil, hydrogenated cottonseed oil, hydrogenatedsunflower oil, and hydrogenated soybean oil; and free fatty acids andtheir salts. Examples of suitable fatty acid esters include sucrosefatty acid esters, mono, di, and triglycerides, glyceryl behenate,glyceryl palmitostearate, glyceryl monostearate, glyceryl tristearate,glyceryl trilaurylate, glyceryl myristate, GLYCOWAX-932, lauroylmacrogol-32 glycerides, and stearoyl macrogol-32 glycerides. Examples ofsuitable phospholipids include phosphotidyl choline, phosphotidylserene, phosphotidyl enositol, and phosphotidic acid. Examples ofsuitable waxes include camauba wax, spermaceti wax, beeswax, candelillawax, shellac wax, microcrystalline wax, and paraffin wax; fat-containingmixtures such as chocolate; and the like.

Suitable meltable polymers include polyethylene oxide, polyvinyl acetateand polycapralactone.

In one embodiment, the discontinuous coated region may contain acarbohydrate which melts and flows below 200° C., preferably below 150°C., e.g., “meltable”. Suitable meltable carbohydrates includepolysaccharides such as polyfructose, polydextrose, inulin, hydrogenstarch hydrosylate; isomalt or sugar alcohols such as xylitol, sorbitolerythritol and mixtures thereof.

In one embodiment, the discontinuous coated region is applied as asolvent based solution, and the solvent is subsequently dried off afterapplication to the dosage form. The solvent may comprise ethanol,isopropyl alcohol or acetone. In another embodiment the solutioncomprises a hydro-alcoholic system, combining alcohol with water. Thesolution can comprise the polymer, carbohydrate, plasticizer, wax,active ingredient and mixtures thereof.

In another embodiment the discontinuous coated region comprises agelling material, or a material that solidifies into a gel upondeposition. The discontinuous coated region is then dried afterdeposition to remove the water, solvent or combination of both. Suitablegelling materials may include gelatin, pectin, gellan gum, carrageenan,and xanthan gum. Suitable water soluble film forming polymers for use inthe discontinuous coated region include but are not limited tohydroxypropyl cellulose, hypromellose, methylcellulose, pullulan,modified starches, and hydroxyethylcellulose.

One preferred process of manufacturing intermediate dosage form beginsby compressing or compacting a tablet core into the desired shape of themedicament. As used herein, “compact, compacting, or compacted” and“compress, compressing, or compressed” may be used interchangeably todescribe the commonly used process of compacting powders into tabletsvia conventional pharmaceutical tableting technology as well known inthe art. One typical such process employs a rotary tablet machine, oftenreferred to as a “press” or “compression machine”, to compact thepowders into tablets between upper and lower punches in a shaped die.This process produces a core having two opposed faces, formed by contactwith an upper and lower punch, and having a belly band formed by contactwith a die wall. Typically such compressed tablets will have at leastone dimension of the major faces at least as long as the height of thebelly band area between the major faces. Alternately, processes havebeen disclosed in the prior art to enable the “longitudinal compression”of tablet cores. When longitudinally compressed tablets are employed, ithas been found that an aspect ratio (height between the major faces towidth or diameter of the major faces) from about 1.5 to about 3.5, e.g.,about 1.9 facilitates handling.

Tablets are typically compacted to a target weight and “hardness”.Hardness is a term used in the art to describe the diametrical breakingstrength as measured by conventional pharmaceutical hardness testingequipment, such as a Schleuniger Hardness Tester. In order to comparevalues across differently sized tablets, the breaking strength isnormalized for the area of the break (which may be approximated astablet diameter times thickness). This normalized value, expressed inkp/cm2, is sometimes referred in the art as “tablet tensile strength.” Ageneral discussion of tablet hardness testing is found in Leiberman etal., Pharmaceutical Dosage Forms—Tablets, Volume 2, 2nd ed., MarcelDekker Inc., 1990, pp. 213-217, 327-329, which is incorporated byreference herein.

The medicaments manufactured according to the present invention,therefore, provide the desired shape, swallowability and appearance fora solid dosage form. Further, the dosage form of the invention providesimproved onset of dissolution and disintegration, while not compromisingswallowability of the dosage form. Use of the discontinuous coatedregions in accordance with the invention permits the ability to addactives, colors, flavors, sensates and textures; impart improvedswallowability, perception of speed, taste masking, and visualrecognition to aid in product selection.

It will become apparent to those skilled in the art that variousmodifications to the preferred embodiments of the invention can be madeby those skilled in the art without departing from the spirit or scopeof the invention as defined by the appended claims.

EXAMPLES

Formula, Preparation Procedure and Viscosity for Polymers Employed toPrepare Discontinuous Coated Regioned Tablets

Example 1: Preparation of Gelatin Solution

TABLE 1 Formula(s) for Gelatin Solution: Formula A Formula B MaterialAmount (g) w/w (%) Amount (g) w/w (%) Polysorbate 80 4.0 0.9 4.0 1.1(Tween ® 80) Purified water 302.0 69.7 233.3 64.0 Gelatin 220 Bloom 94.021.7 94.0 25.8 (bone) Color solution 33.3 7.7 33.3 9.1 TOTAL 433.3 100.0364.6 100.0

Preparation and Viscosity Testing Procedure:

-   -   1. Added polysorbate 80 and purified water to suitable glass        bottle with screw cap. Mixed with magnetic stir bar until        completely dissolved.    -   2. Added gelatin and allowed to rest at room temperature for 60        minutes to bloom.    -   3. Added color solution, stirred manually with metal spatula to        distribute color, capped bottle, and placed in 55° C. oven        overnight.    -   4. Determination of viscosity was performed with a Brookfield        DV-II Pro using the small sample adapter and a suitable spindle:        -   a. Water jacket temperature—55° C.        -   b. Speed—30 rpm.

Example 2: Preparation of Hypromellose Solution

TABLE 2 Formula for Hypromellose Solution: Formula C Material Amount (g)w/w (%) Hypromellose(Pharmacoat ® 603^(a)) 90 25 Purified water 269 75TOTAL 359 100 ^(a)Commercially available from Shin-Etsu Chemical

Preparation and Viscosity Testing Procedure:

-   -   1. Added hot purified water (80-90° C.) to suitable stainless        steel pot with standard mixer and impeller.    -   2. Added Hypromellose (also known as hydropropylmethylcellulose,        or HPMC) slowly and mixed with vortex until dispersed.    -   3. Set mixer to slowest speed, covered with foil, and mixed        overnight. Solution was translucent the next day with no        indication of foam.    -   4. Lower concentrations were prepared by dilution with purified        water.    -   5. Determination of viscosity was performed with a Brookfield        DV-II Pro using the small sample adapter and suitable spindles:        -   a. Water jacket temperature—25° C.        -   b. Speed—30 rpm.

Example 3: Preparation of Hydroxypropylcellulose (HPC) Solution

TABLE 3 Formula for Hydroxypropylcellulose Solution: Formula D MaterialAmount (g) w/w (%) Hydroxypropyl cellulose (Klucel ™ EXF^(b)) 60 16Purified water 315 84 TOTAL 375 100B: Commercially Available from the Ashland Corporation

Preparation and Viscosity Testing Procedure:

-   -   1. Added hot purified water (80-90° C.) to suitable stainless        steel pot with stand mixer and impeller.    -   2. Added HPC slowly and mixed with vortex until dispersed.    -   3. Set mixer to slowest speed, covered with foil, and mixed        overnight. Solution was translucent the next day with no        indication of foam.    -   4. Lower concentrations were prepared by dilution with purified        water.    -   5. Determination of viscosity was performed with a Brookfield        DV-II Pro using the small sample adapter and suitable spindles:        -   Water jacket temperature—25° C.        -   Speed—30 rpm.

The results of the viscosity testing for Examples 1-3 are set forthbelow and in FIG. 17.

TABLE 4 Viscosity Polymer Concentration (%) Viscosity (cP) SpindleGelatin 21.7 159.9 SC4-31 Solution 25.8 411.4 SC4-31 HPMC 5 8.30 SC4-18Solution 10 50.2 SC4-18 13 119.0 SC4-31 16 259.9 SC4-31 20 999.8 LV4 252559 LV4 HPC 6 53.9 SC4-18 Solution 8 171.0 SC4-31 9 254.9 SC4-31 10313.9 SC4-31 12 765.8 SC4-31 14 1620 LV4 16 2499 LV4

Example 5: Preparation of Tablet Core

TABLE 5 Formula for Placebo Tablet Core: Formula F Material Amount (g)w/w (%) Lactose monohydrate (Fast Flo ® 316) 2,587.0 49.75Microcrystalline cellulose (Avicel ® PH 102) 2,587.0 49.75 Magnesiumstearate 26.0 0.50 TOTAL 5,200.0 100

Procedure:

-   -   1. The magnesium stearate was passed through a 35 mesh screen        with 10 grams of the microcrystalline cellulose.    -   2. The remaining microcrystalline cellulose was charged into a        16-qt. v-shell blender.    -   3. The magnesium stearate was layered and preblended on top of        microcrystalline cellulose.    -   4. The lactose monohydrate was layered on top of magnesium        stearate and preblended.    -   5. The mixture was blended for 5 minutes.    -   6. Tablets were compressed using a Natoli® NP-RD10 tablet press        and Kinematics & Controls Corp. model 4400 vacuum powder filler        through the following steps:        -   a. 580 mg of blended material was dispensed into weigh boat            with vacuum powder filler.        -   b. Material was transferred from weigh boat to dye with            custom dye extender attached.        -   c. The tablet was compressed until upper punch contacted dye            extender            -   i. Target tablet weight—570 mg (accounting for material                loss)            -   ii. Target tablet length—0.6590″ (16.7 mm).

Example 6: Preparation of Subcoat for Tablets

TABLE 6 Formula for Tablet Subcoat: Formula G Material Amount (g) w/w(%) Hypromellose* (Methocel ® E5) 138 8.21 Castor oil (USP) 0.562 0.03Purified water 1,542 91.76 TOTAL 1,680.562 100.00 *Hypromellose: Alsolabeled hydroxypropylmethylcellulose

Procedure for Solution Preparation and Tablet Coating Using the Formulain Table 6.

-   -   1. Approximately half of the purified water was heated to        80-90° C. in a suitable vessel.    -   2. The hydroxypropylcellulose (hypromellose) was slowly added to        the water with vortex.    -   3. The remaining room temperature water was added, followed by        the castor oil.    -   4. The solution was covered with foil and continued mixing        overnight on lowest speed.    -   5. 2,250 g of tablets was charged into O'Hara Labcoat 1 with 15″        coating pan.    -   6. Sprayed 1,191 g of coating solution (4.6% weight gain):        -   a. Nozzle—1.2 mm        -   b. Aircap—2.7 mm        -   c. Exhaust air—51.5° C.        -   d. Air volume—150 cfm        -   e. Pan speed—8.9 rpm        -   f. Atomization air—20.3 psi        -   g. Pattern air—26.2 psi        -   h. Spray rate—15 g/min.

Example 7: Procedure for Application of Discontinuous Coated Regions

Part A: Application of Gelatin Discontinuous Coated Regions in ThreePortions

Description of Discontinuous Coated Region Configuration:

The compressed and subcoated caplet cores from Example 6 were used toapply various discontinuous coated regions across the small axis. Thegelatin solution from Example 1 (Table 1) was used. The discontinuouscoated regions completely covered the section of the core utilizing aQualicaps Bench-Top Capsule-Sealer (S-1). A single discontinuous coatedregion was applied across the center portion of the caplet, and twoindependent discontinuous coated regions were applied across the endcaps, wherein the discontinuous coated region partially covered theangled portion of the end, and covered the round portion where the angleend meets the side body.

Part B: Procedure for Application of Discontinuous Coated Regions

-   1. The jacket of the gelatin pan is filled with heat transfer media    (300 mL propylene glycol) and the heater is inserted into the base    of the pan. The gelatin pan is then positioned on the pan base    inside the system and the temperature sensor (thermocouple) is    inserted into the port on the top of the pan.-   2. The discontinuous coated regioning wheels are assembled and    installed to apply the discontinuous coated region to a specified    position on the caplet. The discontinuous coated region thickness,    configuration, and location can be adjusted by using different    wheels and spacer combinations. The doctor blades must also be    selected and affixed in the correct locations, and the    offset/lift-height must be set by adjusting the height of the deck    plate using a knurled knob on the left side of the unit.-   3. The system is powered on and the temperature controller is set to    57° C. The gelatin pan is manually raised into the “full up”    position, activating the in-position switch causing the    discontinuous coated regioning wheels to spin and the heater to    activate. The gelatin pan is left in this position and the heat    transfer media allowed to heat until reaching the set point    temperature where it is maintained.-   4. The gelatin pan is then manually lowered into the “down” position    and gelatin is filled into the pan up to the fill mark. The gelatin    pan is then returned to the “full up position”, now partially    submerging the bottom of the discontinuous coated regioning wheels    in the gelatin solution (and reactivating the spinning of the    discontinuous coated regioning wheels cartridge heater). The    discontinuous coated regioning wheels are allowed to warm, spinning    in the gelatin solutions, for 5 minutes prior to commencing    discontinuous coated regioning.-   5. The Caplets (from Example 6) are loaded into a carrier tray and    placed in the start location on the top of the system. ‘Start’ is    pressed on the front panel, and the carrier is carried, by means of    a flight on a chain, along the carrier path, passing the contained    caplets over the discontinuous coated regioning wheels which spin at    60 RPM counter to the movement direction of the carrier (while    viewing the system from the front, the carrier moves from left to    right, and the coating wheels spin counter-clockwise).-   6. The carrier tray, containing the discontinuous coated regioned    dosage forms, is set in a drying rack to dry for at least 1 hour.

Example 8: Addition of Discontinuous Coated Regions Providing Sweetenerand Cooling

The application procedure used in Example 7, Part B was utilized. 0.5 gof sucralose is added to the hypromellose solution in Example 2, and 0.1g of yellow dye is added. In addition, 0.5 g of Cooler #2 (Serial Number069450), commercially available from the International Flavors andFragrances Corporation, is added to the HPC Solution in Example 3. Inaddition, 0.1 g of blue dye is added. Three solutions are then appliedto the subcoated caplet cores from Example 6. The Hypromellose solutioncontaining sucralose is applied to one end, the Gelatin solution fromExample 1 is added to the center, and the HPC solution containing Cooler#2 is added to the third end. This sample provides for a release ofthree types of discontinuous coated regions, proving three benefits,including sweetness, ease of swallowability and a cooling sensate.

Example 9: Preparation of Melted Discontinuous Coated Region Material

200 g of Polyethylene glycol 8000 is heated to 80° C. and melted. Anadditional 4 g of Polyethylene Oxide WSR-301 (Molecular weight4,000,000) is added and melted. 0.2 g of red colorant is added. Themelted material mixture is applied in 3 separate discontinuous coatedregion structures and allowed to harden at room temperature. These threediscontinuous coated regions add lubricity to a tablet upon hydrationwhen swallowing, without the need to add excessive levels of coatingmaterial which may affect disintegration of the dosage form. Theprocedure in Example 7 is utilized, except the temperature controller isset to 70° C.

In accordance with the present invention, discontinuous coated regionshaving various configurations are used to provide benefits topharmaceutical dosage forms. The discontinuous coated regions providethe ability to vary the types of materials used in the dosage form. Inaddition, discontinuous coated regions are proposed for use oncompressed caplets or tablets. In one embodiment a compressed tablet iscoated (or sub-coated) prior to the application of the discontinuouscoated region; which may improve ease of swallowing or adherence of thediscontinuous coated region.

Embodiment 1: Flavorings and Sensates in Tablet Discontinuous CoatedRegions

In this embodiment the discontinuous coated regions which are added tothe surface of the caplet contain at least one flavoring or sensate. Thesensate may contain a cooling material, a warming material or analternative sensate. In one version of this embodiment the dosage formhas multiple discontinuous coated regions; for example one discontinuouscoated region which contains a sweetener, one discontinuous coatedregion which contains a warming sensate and one discontinuous coatedregion which contains a cooling sensate. In another version of thisembodiment, the discontinuous coated region contains an acidulant suchas citric acid, malic acid or fumaric acid. In another version of thisembodiment, one discontinuous coated region contains sodium bicarbonateand another discontinuous coated region contains citric acid; creating acombined acid couple (“fizzing action”) upon swallowing. In oneembodiment, the caplet contains a subcoat which contains one flavoringmaterial or sensate and the discontinuous coated region contains aseparate flavor, projecting sequential flavoring experience uponingestion.

Embodiment 2: Swallowability Improvements Through Use of TabletDiscontinuous Coated Regions

In this embodiment the discontinuous coated regions incorporate amaterial which helps to aid in the swallowability, making the formeasier to swallow. This may be through the use of a quickly hydratingpolymer. Alternatively, it may be through the addition of a salivationinducing agent such as an acid or succulence sensate.

Embodiment 3: Angled, Spiralled, or Patterned Tablet DiscontinuousCoated Regions

In this embodiment the discontinuous coated region is applied as at anangle or in a spiraled pattern. This can help to convey an elegant lookor ease of swallowing as the discontinuous coated region is moreuniformly covering the caplet. In order to apply the discontinuouscoated region across the circular width of the form, the discontinuouscoated region may need to be tapered at the top and bottom. In anotherversion of this embodiment the discontinuous coated region itself ispatterned or labelled with product information such as brand, indicia ordose.

Embodiment 4: Speed Perception Through Rapidly Dissolving DiscontinuousCoated Regions and Material Selection

In this embodiment, the speed of dissolution is conveyed through theaddition of a fast dissolving discontinuous coated region or adiscontinuous coated region which comprises openings. Fast dissolvingmaterials may include polymers which disintegrate quickly such aspullulan, starch or HPMC. Openings may show the core underneath thediscontinuous coated region. Optionally, the discontinuous coated regionmay include printed portions which convey speed or depth (such as 3Dcone shapes).

Embodiment 5: Addition of Active Ingredients to Discontinuous CoatedRegion

In this embodiment an active ingredient is added to the discontinuouscoated region. In one version a higher dose active ingredient such asacetaminophen or ibuprofen is contained in the compressed core tabletand a second low dose active ingredient (such as cetirizine ordiphenhydramine) is contained in the discontinuous coated regionportion.

The foregoing examples are not intended to limit the scope of thepresent invention, which may be set out in the claims. In particular,various equivalents and substitutions will be recognized by thoseskilled in the art in view of the foregoing disclosure and these arecontemplated to be within the scope of the invention.

1. A dosage form comprising a substrate and at least one discontinuouscoated region positioned on a surface of the substrate, wherein the atleast one discontinuous coated region is positioned longitudinally onthe substrate, wherein said at least one discontinuous coated regionconfers an observable benefit to its user.
 2. The dosage form of claim1, wherein said at least one discontinuous coated region affects atleast one sense of said user, wherein said at least one sense isselected from group consisting of hearing, sight, touch, smell, andtaste.
 3. The dosage form of claim 1, wherein said at least onediscontinuous coated region comprises at least one agent selected fromthe group consisting of sensate, salivant, flavor and sweetener.
 4. Thedosage form of claim 1, wherein said at least one discontinuous coatedregion aids swallowability of said dosage form.
 5. The dosage form ofclaim 1, wherein said at least one discontinuous coated region comprisesat least one lubricious material.
 6. The dosage form of claim 1, whereinsaid at least one discontinuous coated region comprises a visualselected from the group consisting of configuration, color and markingthat conveys attributes of the dosage form to said user.
 7. The dosageform of claim 1, wherein at least two discontinuous coated regions arepositioned on the surface of the substrate.
 8. The dosage form of claim1, wherein the substrate is cylindrical in shape.
 9. The dosage form ofclaim 8, wherein the at least one discontinuous coated regionconcentrically surrounds the surface of substrate.
 10. The dosage formof claim 9, wherein the substrate is angled at one end, and wherein thediscontinuous coated region covers a portion of the angled end. 11.(canceled)
 12. The dosage form of claim 1, wherein the substratecomprises at least one active agent.
 13. The dosage form of claim 1,wherein at least three to at least ten discontinuous coated regions arepositioned on the surface of the substrate.
 14. A method of making adosage form, comprising: (a) preparing a substrate; and (b) positioninga discontinuous coated region on a surface of the substrate.
 15. Themethod of claim 14, wherein the at least one discontinuous coated regionis extrusion coated on the substrate.
 16. The method of claim 14,wherein the at least one discontinuous coated region is screen coated onthe substrate.
 17. The method of claim 14, wherein the at least onediscontinuous coated region is printed on the substrate.
 18. The methodof claim 14, wherein the at least one discontinuous coated region isbrush coated on the substrate.
 19. The method of claim 14, wherein theat least one discontinuous coated region is sprayed on the substrate.20. The method of claim 14, wherein the at least one discontinuouscoated region is painted on the substrate.
 21. The method of claim 14,wherein the at least one discontinuous coated region is 3D printed onthe substrate.
 22. The method of claim 14, wherein the at least onediscontinuous coated region comprises a material selected from the groupconsisting of polymers, meltable carbohydrates, fats, fatty acid esters,phospholipids, waxes, and gelling material, wherein the fats areselected from the group consisting of hydrogenated vegetable oilsselected from cocoa butter, hydrogenated palm kernel oil, hydrogenatedcottonseed oil, hydrogenated sunflower oil, and hydrogenated soybeanoil; and free fatty acids and their salts. wherein the fatty acid estersare selected from the group consisting of sucrose fatty acid esters,mono, di, and triglycerides, glyceryl behenate, glycerylpalmitostearate, glyceryl monostearate, glyceryl tristearate, glyceryltrilaurylate, glyceryl myristate, GLYCOWAX-932, lauroyl macrogol-32glycerides, and stearoyl macrogol-32 glycerides, wherein thephospholipids are selected from the group consisting of phosphotidylcholine, phosphotidyl serene, phosphotidyl enositol, and phosphotidicacid, wherein the waxes are selected from the group consisting ofcamauba wax, spermaceti wax, beeswax, candelilla wax, shellac wax,microcrystalline wax, and paraffin wax, wherein the polymers areselected from the group consisting of polyethylene oxide, polyvinylacetate and polycapralactone; and water soluble film forming polymersselected from hydroxypropyl cellulose, hypromellose, methylcellulose,pullulan, modified starches, and hydroxyethylcellulose, wherein thecarbohydrate is selected from the group consisting of polysaccharidesselected from polyfructose, polydextrose, inulin, hydrogen starchhydrosylate; isomalt; and sugar alcohols selected from as xylitol,sorbitol erythritol and mixtures thereof, and wherein the gellingmaterial is selected from the group consisting of gelatin, pectin,gellan gum, carrageenan, and xanthan gum.
 23. The dosage form of claim1, wherein the at least one discontinuous coated region comprises atape.
 24. The dosage form of claim 1, wherein the at least onediscontinuous coated region comprises a preformed discontinuous coatedregion.
 25. The dosage form of claim 1, wherein the at least onediscontinuous coated region comprises an active agent.
 26. The dosageform of claim 1, wherein the substrate and the at least onediscontinuous coated region each comprise an active agent.
 27. Thedosage form of claim 26, wherein the substrate releases active agent ata rate different from the release rate of active agent from the at leastone discontinuous coated region.
 28. The dosage form of claim 26,wherein the active agent in the substrate is different from the activeagent in the at least one discontinuous coated region.
 29. The dosageform of claim 26, wherein the active agent in the substrate ischemically incompatible with the active agent in the at least onediscontinuous coated region.
 30. The dosage form of claim 1, wherein theat least one discontinuous coated region comprises at least one productselection indicia integrated with the at least one discontinuous coatedregion, wherein said product selection indicia assists a consumer withdetermining whether or not the product is appropriate for the consumer'spurchase or use.
 31. The dosage form of claim 30, wherein the at leastone product selection indicia is selected from the group consisting ofan alphanumeric graphic, a pictorial graphic, a color, brand, logo,color, name of drug, location of symptoms, symptoms treated, time of dayfor use, drowsy/non-drowsy, form, flavor and combinations thereof. 32.The dosage form of claim 30, wherein said dosage form comprises at leasttwo product selection indicia integrated with the at least onediscontinuous coated region.
 33. The dosage form of claim 30, whereinsaid dosage form comprises from two to ten product selection indiciaintegrated with the at least one discontinuous coated region.
 34. Anapparatus for applying a circumferential discontinuous coated region ona surface of a tablet-shaped substrate, comprising: a fixture, whereinsaid fixture contains movable pins, wherein said movable pins engagefeatures on opposing surfaces of said tablet-shaped substrate; a movablesurface in close proximity to said fixture; and a means for applyingcoating solution to said movable surface; wherein rotation of saidmovable surface induces rotation and subsequent circumferentialapplication of said coating solution to said tablet-shaped substrate.35. An apparatus for applying a circumferential discontinuous coatedregion on a surface of a caplet-shaped substrate, comprising: a fixture,wherein said fixture contains one or more drive rings; a movable surfacein close proximity to said fixture; and a solution bath for applyingcoating solution to said movable surface; wherein rotation of saidmovable surface induces rotation and subsequent circumferentialapplication of said coating solution to said caplet-shaped substrate;and wherein said one or more drive rings disrupt a boundary fluid layerto assist rotation of said caplet-shaped substrate.
 36. An apparatus forapplying a circumferential discontinuous coated region on a surface of anon-rounded horizontally caplet-shaped substrate, comprising: a fixture;a movable surface in close proximity to said fixture; a moving abutmentface; and a solution bath for applying coating solution to said movablesurface; wherein rotation of said movable surface induces rotation andsubsequent circumferential application of said coating solution to saidnon-rounded horizontally caplet-shaped substrate; and wherein saidmoving abutment face runs along the movable surface prior to saidfixture to assist with rolling of said non-rounded horizontallycaplet-shaped substrate.
 37. An apparatus for applying one or morediscontinuous coated regions on a surface of a substrate, comprising anapplicator, wherein an end face of said applicator comprises openingssuch that when said applicator comprises fluid, air can escape from saidopenings, and wherein a surface area of said end face of said applicatorand spacing of said openings are selected to control a volume of coatingmaterial passing across said end face of said applicator.
 38. Theapparatus of claim 37, further comprising: a heated bath; a fluidreservoir; and a means for immersing said applicator in said heatedbath; a means for charging said applicator with said fluid; a means forplacing said applicator charged with fluid in communication with saidsubstrate; and a means for discharging said fluid from said applicatoronto said substrate.
 39. An apparatus for applying two or more distinctdiscontinuous coated regions on a substrate, comprising two or moreapplicators of claim
 37. 40. The apparatus of claim 37, furthercomprising: a pump means, wherein said pump means injects said fluiddirectly to said end face of said applicator.
 41. The apparatus of claim38, further comprising: a carrier for said substrate, wherein saidcarrier for said substrate permit(s) axes of freedom of said substratesuch that the surface of said substrate conforms to said openings.